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Herzreparatur mit Herzmuskelpflaster aus Stammzellen – Umsetzung eines präklinischen Konzeptes in die klinische Prüfung
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Interference with platelet-derived growth factor-induced activation of vascular smooth muscle cells and stenosing vascular remodeling
No full textGefäß- und ihre Folgeerkrankungen stellen die häufigste Todesursache in der
westlichen Welt dar. Daher sind Strategien zur Reduzierung stenosierender,
vaskulärer Umbauprozesse therapeutisch wünschenswert. Dies schließt die genaue
Kenntnis der zugrunde liegenden zellulären und molekularen Mechanismen von
Gefäßerkrankungen, wie der Atherosklerose und der Restenose, mit ein.
Experimentelle Daten stützen die Annahme, dass die Platelet-derived Growth
Factor (PDGF)-Signaltransduktion von zentraler Bedeutung im Rahmen dieser
Prozesse ist. Verschiedene Aspekte stenosierender, vaskulärer
Gewebeumbauprozesse, insbesondere Komponenten der PDGF-Signaltransduktion,
wurden in der vorliegenden Habilitationsschrift untersucht. So konnte in der
Originalarbeit 1 gezeigt werden, dass 17-beta Östradiol die PDGF-BB-induzierte
Signaltransduktion und Zellfunktionen in glatten Gefäßmuskelzellen in vitro
signifikant beeinflusst. Während ein Einfluss auf die PDGF β-Rezeptor
Expression, Liganden-induzierte Rezeptor-Tyrosinphosphorylierung sowie
Rekrutierung zytosolischer Bindungsproteine ausgeschlossen wurde, bestand eine
konzentrationsabhängige Reduktion der PDGF-BB-induzierten DNA-Synthese und
Zellmigration. Dieser inhibitorische Effekt durch 17-beta Östradiol wurde
downstream des PDGF β-Rezeptors durch Verminderung der Aktivierung des kleinen
GTP-bindenden Proteins rac-1 vermittelt. So führte auch die transiente
Überexprimierung von dominant-negativem rac-1 sowie ein rac-1 Inhibitor zur
Hemmung der PDGF-BB-induzierten Migration glatter Gefäßmuskelzellen. Diese
Daten bieten eine mögliche molekulare Erklärung vaskuloprotektiver Effekte von
Östrogenen. Die Bedeutung antiretroviraler Therapeutika für Zellfunktionen
glatter Gefäßmuskelzellen in vitro sowie im Rahmen experimentell induzierter
vaskulärer Gewebeumbauprozesse in vivo wurde in den Originalarbeiten 2 und 3
untersucht. Während die Analyse der direkten Effekte von Ritonavir auf glatte
Gefäßmuskelzellen eine Interferenz mit PDGF-BB-induzierter
Tyrosinphosphorylierung des PDGF β-Rezeptors sowie der DNA-Synthese sowie
Zellmigration und damit einen Wachstum-inhibierenden Einfluss von Ritonavir
außerhalb von zytotoxischen und pro-apoptotischen Effekten zeigte
(Originalarbeit 2), bestand eine Progression der vaskulären Umbauprozesse und
eine Hemmung endothelialer Regenerationskapazität durch HAART in einem
Tiermodell vaskulärer Schädigung (Originalarbeit 3). Somit stehen potentiell
direkte, protektive Effekte in vitro unerwünschten Effekten in vivo gegenüber.
Diese Daten zeigen, dass zum einen anti-restenotische Eigenschaften von
Ritonavir auf einer zellulären und funktionellen Ebene bestehen, zum anderen,
dass HAART möglicherweise negativen Einfluss auf den endothelialen
Heilungsprozess bzw. den vaskulären Umbau nach Gefäßverletzung besitzt. Neben
der Liganden-Exposition wird die Aktivität von Rezeptortyrosinkinasen wie dem
PDGF β-Rezeptor maßgeblich durch Protein-Tyrosin-Phosphatasen (PTPs)
reguliert. Dies beinhaltet auch die Beeinflussung der nachgeschalteten
Signaltransduktion sowie zellulärer Funktionen. Die Bedeutung von PTPs in
stenosierenden, vaskulären Umbauprozessen wurde in Modellen der vaskulären
Schädigung in vivo analysiert. Zum einen konnte gezeigt werden, dass PTPs
zeit- und schicht-spezifisch während der Neointimaentwicklung reguliert wurden
und dass dies die Aktivität des PDGF β-Rezeptors beeinflusste. Hierbei scheint
insbesondere die transiente Herunterregulierung der PTP DEP-1 von Bedeutung zu
sein (Originalarbeit 4). Zum anderen wurde die Hypothese getestet und
bestätigt, dass die Applikation von Antioxidantien durch Hemmung der Oxidation
des active-site Cysteins in der katalytischen Domäne PTPs (re-)aktiviert, was
zur Antagonisierung des PDGF β-Rezeptors in vivo führte und konsekutiv die
Neotintimaentwicklung nach Gefäßverletzung reduzierte (Originalarbeit 5).
Hierin liegt möglicherweise ein therapeutischer Ansatz zur Modifizierung von
dysregulierten Gewebeumbauprozessen, die mit gesteigerter Aktivität von
Rezeptortyrosinkinasen vergesellschaftet sind.Vascular diseases and their consequences represent the most frequent cause of
death in the Western world. Thus, strategies to reduce stenosing, vascular
remodeling processes are of high therapeutic value. A prerequisite for
therapeutic strategies is the in-depth knowledge of underlying cellular and
molecular mechanisms in vascular disease, such as atherosclerosis and
restenosis. Experimental data underline the assumption that platelet-derived
growth factor (PDGF)-singal transduction is of crucial importance for these
processes. A variety of aspects of stenosing, vascular remodeling processes,
in particular components of PDGF-signal transduction, have been analyzed in
this work. Data of article no. 1 demonstrate that 17-beta estradiol (E2)
significantly impacts on PDGF-BB-induced signal transduction and cellular
responses in vascular smooth muscle cells in vitro. While an impact of E2 on
PDGF β-receptor expression, ligand-induced receptor tyrosine-phosphorylation,
and recruitment of cytosolic binding proteins was excluded, a concentration-
dependent reduction of PDGF-BB-induced DNA-synthesis and cell migration was
demonstrated. This inhibitory effect of E2 was induced by reduced activation
of the small GTP-binding protein rac-1. In addition, transient overexpression
of dominant-negative rac-1, and a rac-1 inhibitor led to impairment of PDGF-
BB-induced migration of vascular smooth muscle cells. Taken together, these
observations offer a molecular explanation for the vasoprotective effects of
estrogens. The impact of anti-retroviral drugs on cellular functions in
vascular smooth muscle cells in vitro, and during experimentally induced
vascular remodeling processes in vivo, were evaluated in articles no. 2 and 3.
While analysis on direct effects of Ritonavir on vascular smooth muscle cells
demonstrated an interference with both PDGF-BB-induced tyrosine-
phosphorylation of the PDGF β-receptor and DNA-synthesis, and with cell
migration, and thus demonstrating a growth-inhibiting impact of Ritonavir
without exhibiting cytotoxic and apoptotic effects (article no. 2), a
progression of vascular remodeling processes and an inhibition of endothelial
regenerative capacity was observed due to treatment with highly-active anti-
retroviral therapy (HAART) in an animal model of vascular injury (article no.
3). Thus, potentially direct, protective effects in vitro are facing unwanted
effects in vivo. These data show that on one hand anti-restenotic properties
of Ritonavir are evident on a cellular and functional level, while on the
other hand HAART possibly possesses negative impact on the endothelial healing
process and on vascular remodeling following vascular injury. Besides ligand
binding the activity of receptor tyrosine kinases, such as the PDGF
β-receptor, is critically controlled by protein tyrosine phosphatases (PTPs).
This involves also the regulation of downstream signal transduction processes
and cellular functions. The role of PTPs in stenosing, vascular remodeling
processes was investigated in models of vascular injury in vivo. It was
demonstrated that PTPs were time- and layer-specifically regulated during the
process of neointima formation, along with changes of the PDGF β-receptor. In
particular, the transient down-regulation of the PTP DEP-1 seemed to be
crucial for the tissue remodeling process (article no. 4). Furthermore, the
hypothesis that application of antioxidants leads to inhibition of oxidation
of the active-site cysteine in the catalytic domain of PTPs, thus resulting in
(re-)activation of PTPs, was tested and eventually verified. Antioxidants led
to antagonizing of the phosphorylation of the PDGF β-receptor in vivo, and
consecutively to reduced neointima formation following vascular injury
(article no. 5). These data implicate a therapeutic approach to modify
dysregulated tissue remodeling processes that are associated with increased
activity of receptor tyrosine kinases
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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